中文摘要：

目的探讨间充质干细胞（MSCs）治疗肝移植术后难治性急性移植物抗宿主病（GVHD）的疗效和安全性。方法回顾性分析中山大学附属第三医院肝脏移植中心1例应用第三方脐带来源的MSCs治疗肝移植术后激素治疗无效的急性GVHD患者的临床资料。结果患者男性,60岁,因＂原发性肝癌、乙肝肝硬化＂在我院行同种异体原位肝移植术,供受者血型相同。术后免疫抑制方案为糖皮质激素联合他克莫司。术后19 d患者出现发热、全身皮疹,并出现白细胞减少症、口腔溃疡和腹泻,但肝功能正常。皮肤活检病理组织学检查见淋巴细胞浸润,结合临床表现诊断为GVHD。给予停用免疫抑制剂、大剂量糖皮质激素冲击治疗、营养支持、大剂量丙种球蛋白等治疗后,患者病情无好转,持续发热,于术后第40天开始周围静脉输注脐带来源的MSCs治疗,治疗3 d后患者体温和白细胞恢复正常,腹泻好转。MSCs治疗方案为：细胞数5×107/次,每次间隔1周,共3次。患者无不适及其他并发症发生,GVHD获得完全缓解,于术后55 d痊愈出院,随访20个月未观察到MSCs输注相关的不良反应发生,未发现肝癌复发和MSCs相关的恶性肿瘤发生。结论输注体外培养扩增的第三方来源的MSCs是治疗肝移植术后激素治疗无效的急性GVHD的有效措施,值得进一步研究。

英文摘要：

Objective To explore the efficacy and safety of mesenchymal stem cells（ MSCs）treatment in severe refractory acute graft-versus-host disease（ GVHD） after liver transplantation.Method Retrospective analysis of the clinical data of a case of the third source umbilical cord MSCs treatment of acute GVHD after glucocorticoids therapy failed. Results A 60-year-old man was performed allograft orthotopic liver transplantation because of ＂ hepatocellular carcinoma and hepatitis B cirrhosis＂ in our hospital. The blood type of the recipient and donor was the same. The postoperative immunosuppressant scheme was glucocorticoids combined with tacrolimus. The patient appeared fever,skin rashes,white blood cells decreasing,oral ulcer and diarrhea on postoperative day 19,but liver function was normal. The pathological examination of skin biopsy showed lymphocytes infiltration. Then he was diagnosed of GVHD combined with the clinical manifestation. The patient still had persistent fever and exhibited,no remission of the condition after immunosuppressants withdraw,high-dose glucocorticoids impact treatment,nutritional support and large dose of gamma globulin treatment. Thenwe began to use umbilical cord MSCs treatment by peripheral intravenous injection on postoperative day40. After 3 days＇ treatment,the temperature and white blood cells were back to normal,and diarrhea disappeared. The scheme of MSCs treatment was 5 × 107 cells once,and a total of 3 times with a interval of 1 week. The patient had no discomfort and other complications when GVHD was alleviated,and discharged on postoperative day 55. After 20 months of follow-up,no MSCs infusion related adverse reactions and recurrence of liver cancer and the malignant tumor associated MSCs was observed.Conclusion In vitro amplificated MSCs from the third source infusion is an effective measure in treating acute GVHD after liver transplantation when glucocorticoids therapy failed,which deserved further research.